Early detection of disease allows the maximum likelihood of successful treatment and recovery. Furthermore, early detection and localization of the disease permits directed therapy to the site of the disease optimizing the efficiency of the treatment. With an appropriate detection device, the treatment can be monitored, further increasing the efficacy of the applied drugs or other forms of therapy. The ability to target specific diseases can also improve treatment outcomes. Early detection and localization of cancer, the second leading cause of death in the US, can improve patient outcomes. The most common methods used for clinical purposes for detection of cancer are all non-specific, i.e., they cannot distinguish between cancerous or benign tumors and none lead to 100% accurate detection. The available methods all have disadvantages and weaknesses, resulting in high rates of false diagnosis and too low a rate of positive diagnosis, together leading to increased mortality rates. The most common clinical modalities presently available are: (1) X-ray mammography, (2) magnetic resonance imaging (MRI), and (3) ultrasound scanning with (4) positron-emission tomography (PET) an additional option when available.
The measurement of X-ray attenuation provides information on the density of the intervening medium and is FDA approved and the most common device used to detect various forms of disease and, in particular, cancer. It is also responsible for many false-negative and false-positive results. Early stage cancer tumors can be detected but without specificity with regard to benign or cancerous tumors. Artifacts can be caused by healthy tissue and give rise to false positive results. Although the dose is low, there is increasing concern about the exposure to X-rays and radiation in general. Overall, the number of false positives in x-ray imaging of cancer remains high and the x-ray method cannot detect early-stage tumors.
Ultrasound is used to provide a second method for imaging tumors. Ultrasound has excellent contrast resolution but suffers from diminished spatial resolution compared to x-rays and other imaging techniques. Ultrasound is not currently approved by the FDA as a primary screening tool for cancer but is normally used as a follow up to investigate any abnormalities detected during routine. It is a tool often used to confirm suspect areas in x-ray images of breast and ovarian cancer.
MRI is used to follow up on potential problem areas seen during x-ray scans; however, the expense of a MRI scan often prohibits its use. MRI can detect small abnormalities in tissue and is also useful in determining if cancer has metastasized. Dynamic Contrast Enhanced (DCE) MRI potentially distinguishes between benign and cancerous tumors but produces a number of false positives. The expense of MRI limits its application as a screening tool. MRI imaging of cancer often uses magnetic nanoparticles as contrast agents and is an accepted protocol providing standards for the injection of such nanoparticles. Intravascular MRI contrast agents at a dose of about 2-5 mg/kg of nanoparticle weight have been used to detect metastatic lesions.
Because of the importance of early detection of disease, there are a variety of other techniques currently being studied for imaging. These include scintimammography using PET or SPECT, Impedance Tomography, and various forms of RF imaging.
Cancer is currently the second highest cause of death in the United States, second only to heart conditions. In 2009, approximately 570,000 people died of this disease, dominated by lung cancer (26-30%), breast cancer in women (15%) and prostate cancer in men (9%). Breast cancer results in 44,000 deaths a year in the United States; prostate cancer results in over 27,000 deaths. Early detection of cancer is important since discovery of tumors early minimizes the chances for metastatic transfers of the cancer to other parts of the body. Current methods for detecting cancer rely largely on (1) x-ray imaging (such as mammography in women's breast cancer), (2) ultrasound, (3) notice of physical changes, (4) MRI, and (5) PET scans. Routine screening is normally only done in mammography for women and for the genetically susceptible population. A large proportion of cancers are silent killers in that they express their presence only after metastasis and manifestation of severe discomfort. Early detection and treatment is difficult because of this and new approaches are extremely desirable.
Treatment of cancer once it is found can include any of a spectrum of methods, including surgery, chemotherapy, and ablation. Surgical removal of cancer is very effective if the cancer is contained in the primary site and is operable, but depends upon localization of the tumor. Normally, considerably more tissue is removed than the tumor itself in order to assure that all of the cancer is taken. Chemotherapy is the application of anti-cancer drugs and is normally done using injections of drugs that destroy cancer cells at a higher rate than normal cells. Typically chemotherapy is used to destroy fast growing cells and has therefore side effects affecting the digestive system and hair loss. Side effects can be severe with normal chemotherapy since the entire blood system is flooded with the chemicals. This can be particularly severe in young children with rapidly developing brains. Since traditional chemotherapy is non-localized and affects all of the body's organs it has a significant death rate associated with it. Ablation of tumors normally involves low temperature application (cryotherapy), or high temperature application (hyperthermia), to destroy cancer cells. Hyperthermia, as applied to cancer treatment, uses various devices to raise body tissue to sufficiently high temperatures, for example about 113° F. At these temperatures, cancer cells are damaged or killed. However, this must be done with minimal injury to normal tissues. The goal of cryotherapy and hyperthermia treatment is to shrink or eliminate cancerous tumors in the body. The location of the tumor must be ascertained beforehand. Typically, hyperthermia is applied over a much larger area than the known position of the tumor to make sure that the tumor is destroyed. X-rays or other imaging methods are then used to see if the tumor has been destroyed. These techniques have limitations based on sensitivity to tumor size and image contrast.
Hyperthermia is not well established as a clinical tool because studies have shown that the destruction of normal cells is excessive or there is insufficient destruction of localized tumors. A variety of methods for hyperthermia are used today including direct application of heat either localized or whole body through thermal blankets, the use of radio-frequency waves to heat up tissue, the use of optical techniques to use light (in particular infrared light), and heat probes inserted into tumors.
In general, hyperthermia is not normally used as the only therapy option when treating cancer but is combined with other forms of treatment, including radiation therapy, chemotherapy and anti-cancer drugs. Hyperthermia increases cancer cell sensitivity to other modalities, so the combination makes the other modalities more effective. When hyperthermia and radiation therapy are combined, they are often given within an hour of each other. Hyperthermia can also enhance the effects of certain anticancer drugs. The major organs exposed to hyperthermia include the breast, lungs, liver, cervix, and colon. Unfortunately, there is insufficient evidence that the current use of hyperthermia adds to patient survival times.
Hyperthermia is primarily applied locally in order to minimize damage to normal cells and organs not containing cancer. In these cases, the heating is accomplished through application of electromagnetic waves, typically in the hundreds of kHz to MHz, or the use of focused ultrasound. For implementation of these methods, the tumor position and size are predetermined by some imaging methods and the energy for heating is applied either through external means or internal probes. In this approach, the energy is focused in such a way as to minimize damage to normal tissue surrounding the tumor although inevitably damage does occur. This method is similar to cryo-ablation of tumors and removal of tumor cells, or ablation, occurs during the heating. This method is sometimes referred to as endocavitary or interstitial. Heating of larger body areas, including whole body hyperthermia, is used for larger tumors or when cancer has spread through the body. In these cases the body temperature can be raised to 108° F. either by immersion in a thermal bath or by application of RF heating over larger areas as discussed above.
In order to avoid serious side effects, the temperature of the affected regions during hyperthermia must be carefully monitored, commonly done using small inserted thermometers which are placed using various imaging devices. This can be a very painful procedure requiring local anesthesia. Normal tissue must be kept below 111° F. Proper application of hyperthermia is related to the temperature achieved during the treatment, as well as the length of treatment and cell and tissue characteristics. Although the goal of hyperthermia is not to destroy normal tissues by keeping the tissue temperature under 111° F., differences in tissue characteristics may cause hot spots resulting in burns, blisters, discomfort, or pain. Accurate localization of where the hyperthermia is applied can reduce the destruction of normal cells and permit higher concentration of energy applied to the tumor cells.
The standard application of chemotherapy is the direct injection of drugs into the body to treat the cancer. In most applications, one or more drugs are used to treat a variety of cancers and only certain drugs are specific to distinct cancer types. The drugs can be aimed directly at cancer cells or can be aimed at the rapidly growing vascular structure associated with a tumor. Although cancer cells are most affected by these drugs, many other cell types in the body also are harmed. The side effects can be life changing. The brain can suffer severe effects, sometimes referred to as “Chemo Brain,” that can cause confusion and disorientation for years or for life. The effects on young children can cause loss of IQ and life-long memory problems. There may be short or long term skin, hair and intestinal changes. Peripheral neuropathy can also be induced and the resulting peripheral nerve damage can be permanent. Localization of drug concentration and effectiveness would allow a major change in chemotherapy application permitting the use of more advanced and specific drugs while minimizing the side effects of the drug.
In standard methods of application of therapy including hyperthermia and drug delivery, it is necessary to monitor the effects of the therapy by imaging methods that were used to determine the original location of the tumor. This is a very limiting procedure since the tumor had to have substantial size, e.g., several mm in diameter, before it could be detected originally and the knowledge of complete destruction of the tumor is limited by this detection size. Thus the normal method for monitoring the effectiveness of the treatment is to look for reoccurrence of the tumor. This also means that the treatment by hyperthermia or chemotherapy attempts to exceed the need to remove the tumor in order to make sure the therapy has succeeded resulting in increased unnecessary side effects. An effective means of monitoring the therapy would represent a major advance in the field of cancer treatment.